Glioblastoma Multiforme (GBM)Phase 2GBMNCT04587830
ADI-PEG 20 Plus Radiotherapy and Temozolomide in Subjects With Glioblastoma Multiforme
A Phase 2 study testing ADI-PEG 20 and Temozolomide in people with Glioblastoma Multiforme (GBM), run by Polaris Group at 10 sites in 2 countries.
Trial summary
A randomized, double-blind, placebo-controlled study. Weekly ADI-PEG 20 (36 mg/m2) or placebo will be combined with Stupp Protocol (Stupp 2005) radiotherapy and TMZ Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Glioblastoma Multiforme (GBM)
- What is being tested?
- ADI-PEG 20 and Temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 14 Sep 2020to 30 May 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed, histologically confirmed glioblastoma, IDH-wildtype and the WHO Grade 4 of astrocytoma, IDH-mutant by WHO 2021 classification of brain tumors, non-resectable or partially resected or resected.
- Age 20 - 75 years.
- Karnofsky Performance Status (KPS) ≥ 60.
- Expected life expectancy ≥16 weeks.
- Stable or decreasing corticosteroids (5 mg/day dexamethasone or equivalent) within 5 days before the first dose of ADI-PEG 20.
- No prior systemic therapy, immunotherapy, investigational agent, or radiation therapy.
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- Recovered from any prior surgery and no major surgery within 2 weeks of initiating treatment (other than GBM surgery). Surgery for placement of vascular access devices is acceptable.
- Female subjects and male subjects must be asked to use appropriate contraception for both the male and female for the duration of the study and for at least 30 days after the last administration of ADI-PEG 20 or placebo and at least 6 months after the last administration of TMZ. Male partners of female subjects and female partners of male subjects must agree to use two forms of contraception or agree to refrain from intercourse for the duration of the study if they are of childbearing potential. Females of childbearing potential must not be pregnant at the start of the study, and a serum human chorionic gonadotropin (HCG) pregnancy test must be negative before entry into the study. If positive HCG pregnancy test, further evaluation to rule out pregnancy must be performed according to GCP before this subject is deemed eligible. Females not of childbearing potential must be post-menopausal (defined as cessation of regular menstrual period for at least 12 months).
- Informed consent must be obtained prior to study initiation.
- No concurrent investigational studies are allowed.
- Absolute neutrophil count (ANC) ≥ 1500/μL.
- Platelets ≥ 100,000/μL.
- Serum uric acid ≤ 8 mg/dL (with or without medication control).
- Creatinine clearance must be ≥ 40 mL/min/1.73 m2 (calculated using the Cockcroft-Gault equation: calculated creatinine clearance = (140-age (yrs)) × body weight (kg) (×0.85 if female) / 72 × serum creatinine (mg/dl).
- Total bilirubin ≤ 2 x upper limit of normal.
- ALT and AST ≤ 3 x upper limit of normal, unless liver metastases present then ≤ 5 x upper limit normal.
Who cannot join
- Serious infection requiring treatment with systemically administered antibiotics at the time of study entrance, or an infection requiring systemic antibiotic therapy within 7 days prior to the first dose of study treatment.
- Pregnancy or lactation.
- Expected non-compliance.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), cardiac arrhythmia, or psychiatric illness, social situations that would limit compliance with study requirements.
- Subjects with history of another primary cancer, including co-existent second malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present or in the opinion of the investigator will not affect patient outcome.
- Subjects who had been treated with ADI-PEG 20 previously.
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- History of uncontrolled seizure disorder not related to underlying cancer.
- Known HIV positivity, or active hepatitis B infection, or active hepatitis C infection (testing not required).
- Allergy to pegylated compounds.
- Allergy to E. coli drug products (such as GMCSF).
- Allergy to TMZ or any of its components.
- History of hypersensitivity to dacarbazine.
- Placement of Gliadel wafer at surgery.
- Having a co-existing condition requiring systemic treatment with either corticosteroids or immunosuppressive medication.
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
South Korea5 sites
Seoul National University Bundang Hospital
Gyeonggi-do, Seongnam, 13620
Chonnam National University Hwasun Hospital
Hwasun-gun, Jeollanam-do, 58128
Seoul National University Hospital
Seoul, Jongno-gu, 03080
Seoul St. Mary's Hospital, The Catholic University of Korea
Seoul, Seocho-gu, 06591
Severance Hospital Yonsei University
Seoul, Seodaemun-gu, 03722
Taiwan5 sites
Chang Gung Medical Foundation-Kaohsiung
Kaohsiung City, Niaosong Dist, 833401
Chang Gung-Medical Foundation-Keelung (CGMF-KL)
Keelung, Anle Dist, 204201
Mackay Memorial Hospital-Tamsui Branch
New Taipei City, Tamsui Dist, 251404
National Taiwan University Hospital
Taipei, Zhongzheng Dist, 100229
Chang Gung Memorial Hospital, Linkou Branch
Taoyuan, Guishan Dist, 333423
About this study
Official title: Phase 1-2 Trial of ADI-PEG 20 Plus Radiotherapy and Temozolomide in Subjects With Newly Diagnosed Glioblastoma Multiforme (GBM)
A randomized, double-blind, placebo-controlled study. Weekly ADI-PEG 20 (36 mg/m2) or placebo will be combined with Stupp Protocol (Stupp 2005) radiotherapy and TMZ
Read the detailed description
A randomized, double-blind, placebo-controlled study. Weekly ADI-PEG 20 (36 mg/m2) or placebo will be combined with Stupp Protocol (Stupp 2005) radiotherapy and TMZ as noted for the Phase 1 portion. Furthermore, ADI-PEG 20 or placebo treatment may continue after adjuvant TMZ if there is no progressive disease, for up to a total of 2 years of ADI-PEG 20 or placebo treatment. In addition, after 24 weeks (6 cycles) subjects may also continue adjuvant TMZ along with ADI-PEG 20 or placebo, in the absence of disease progression, as noted above, if clinically indicated in the investigator's judgement. MRI is to be performed post-surgery(biopsy), and then at 1, 3 and 6 months after completion of radiotherapy and then every 3 months for up to 24 months.
- Conditions
- Glioblastoma Multiforme (GBM)
- Being tested
- ADI-PEG 20, Temozolomide, Placebo
- Keywords
- argininosuccinate synthetase, arginine, arginine deiminase
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ADI-PEG 20Drug
Investigational Medicine
TemozolomideDrug
Radiotherapy and TMZ are standard front-line therapy for newly diagnosed GBM.
PlaceboDrug
Investigational Medicine
| Study group | Role | What they receive |
|---|---|---|
| ADI-PEG 20 plus Radiotherapy and Temozolomide | Experimental | ADI-PEG 20 Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM)
Radiotherapy Dose: 60 Gy in 30 daily (Monday-Friday) fractions of 2 Gy each; to start within 4 weeks of surgery (diagnostic and/or resection)
Temozolomide Dose: 75 mg/m2 daily during radiotherapy; 150-200 mg/m2 for 5 days every 4 weeks (1 cycle) x 6 cycles during maintenance period Route of Administration: oral or intravenous Receives: Drug: ADI-PEG 20; Drug: Temozolomide |
| Placebo plus Radiotherapy and Temozolomide | Placebo comparator | Placebo Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM)
Radiotherapy Dose: 60 Gy in 30 daily (Monday-Friday) fractions of 2 Gy each; to start within 4 weeks of surgery (diagnostic and/or resection)
Temozolomide Dose: 75 mg/m2 daily during radiotherapy; 150-200 mg/m2 for 5 days every 4 weeks (1 cycle) x 6 cycles during maintenance period Route of Administration: oral or intravenous Receives: Drug: Temozolomide; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
In the ADI-PEG 20 treated arm compared to the placebo arm, and determine if predefined patient subtypes or associated biomarkers uniquely benefit from the treatment
Measured: Through study completion, 2.5 year anticipated
Secondary outcomes (7)
Progression-free survival (PFS)
PFS will be reported as the time subject experience from the start of treatment to disease progression or death, measured in month.
Measured: Through study completion, 2.5 year anticipated
Duration of response (DOR)
DOR is reported as the time from when the tumor begins to respond to treatment (first occurrence of CR or PR) until disease progression or deterioration occurs (diagnosis of disease progression), measured in month.
Measured: Through study completion, 2.5 year anticipated
Tumor response rate
Response rate is usually measured in percentage (%). It represents the proportion of subjects whose tumors achieve partial or complete response among those who received treatment.
Measured: Through study completion, 2.5 year anticipated
Safety and tolerability of ADI-PEG 20
Safety and tolerability in the ADI-PEG 20 treated arm compared to the placebo arm.
Incidence of Treatment-Emergent Adverse Events from first dose to time of progression or death.
The severity of all AEs will be assessed according to the NCI CTCAE Scale version 5.
Measured: Through study completion, 2.5 year anticipated
Pharmacokinetics of ADI-PEG 20
ADI-PEG 20 Plasma Concentrations are measured over time, samples are collected before the dosing, and on week 0, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 28 and 32, then every 4 weeks until week 52 or End of treatment visit.
Measured: Up to week 52 or End of treatment visit
Pharmacodynamics of ADI-PEG 20
Citrulline and Arginine plasma concentrations are measured over time, samples are collected before the dosing, and on week 0, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 28 and 32, then every 4 weeks until week 52 or End of treatment visit.
Measured: Up to week 52 or End of treatment visit
Immunogenicity of ADI-PEG 20
Antibodies for ADI-PEG 20, Anti-PEG antibodies are measured in plasma over time, samples are collected before the dosing, and on week 0, 1, 2, 4, 6, 8, 10, 12, 13, 16, 20, 24, then once a month for three months, followed by once every three months until week 52 or End of treatment visit.
Measured: Up to week 52 or End of treatment visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2020
- Study start14 Sep 2020
- Primary completion28 Feb 2027 (estimated)
- Study completion30 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma Multiforme (GBM)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Polaris Group
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kuo-Chen Wei, M.D., Principal investigator, Chang Gung Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04587830
- Sponsor's protocol ID
- POLARIS2020-001
- Acronym
- GBM
- Status last verified
- Aug 2025
- First submitted
- 4 Sep 2020
- Last updated
- 26 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1-2 Trial of ADI-PEG 20 Plus Radiotherapy and Temozolomide in Subjects With Newly Diagnosed Glioblastoma Multiforme (GBM)
- ClinicalTrials.gov ID
- NCT04587830
- Acronym / sponsor ID
- GBM / POLARIS2020-001
- Conditions
- Glioblastoma Multiforme (GBM)
- Keywords
- argininosuccinate synthetase, arginine, arginine deiminase
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Polaris GroupIndustry (pharma, biotech, devices)
- Study start
- 14 Sep 2020 (actual)
- Primary completion
- 28 Feb 2027 (estimated)
- Study completion
- 30 May 2027 (estimated)
- First posted
- 14 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized, double-blind, placebo-controlled study. Weekly ADI-PEG 20 (36 mg/m2) or placebo will be combined with Stupp Protocol (Stupp 2005) radiotherapy and TMZ
Detailed description
A randomized, double-blind, placebo-controlled study. Weekly ADI-PEG 20 (36 mg/m2) or placebo will be combined with Stupp Protocol (Stupp 2005) radiotherapy and TMZ as noted for the Phase 1 portion. Furthermore, ADI-PEG 20 or placebo treatment may continue after adjuvant TMZ if there is no progressive disease, for up to a total of 2 years of ADI-PEG 20 or placebo treatment. In addition, after 24 weeks (6 cycles) subjects may also continue adjuvant TMZ along with ADI-PEG 20 or placebo, in the absence of disease progression, as noted above, if clinically indicated in the investigator's judgement. MRI is to be performed post-surgery(biopsy), and then at 1, 3 and 6 months after completion of radiotherapy and then every 3 months for up to 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ADI-PEG 20 plus Radiotherapy and Temozolomide | Experimental | Drug: ADI-PEG 20, Drug: TemozolomideADI-PEG 20 Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Radiotherapy Dose: 60 Gy in 30 daily (Monday-Friday) fractions of 2 Gy each; to start within 4 weeks of surgery (diagnostic and/or resection) Temozolomide Dose: 75 mg/m2 daily during radiotherapy; 150-200 mg/m2 for 5 days every 4 weeks (1 cycle) x 6 cycles during maintenance period Route of Administration: oral or intravenous |
| Placebo plus Radiotherapy and Temozolomide | Placebo comparator | Drug: Temozolomide, Drug: PlaceboPlacebo Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM) Radiotherapy Dose: 60 Gy in 30 daily (Monday-Friday) fractions of 2 Gy each; to start within 4 weeks of surgery (diagnostic and/or resection) Temozolomide Dose: 75 mg/m2 daily during radiotherapy; 150-200 mg/m2 for 5 days every 4 weeks (1 cycle) x 6 cycles during maintenance period Route of Administration: oral or intravenous |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Newly diagnosed, histologically confirmed glioblastoma, IDH-wildtype and the WHO Grade 4 of astrocytoma, IDH-mutant by WHO 2021 classification of brain tumors, non-resectable or partially resected or resected.
- Age 20 - 75 years.
- Karnofsky Performance Status (KPS) ≥ 60.
- Expected life expectancy ≥16 weeks.
- Stable or decreasing corticosteroids (5 mg/day dexamethasone or equivalent) within 5 days before the first dose of ADI-PEG 20.
Key exclusion criteria (14 listed)
- Serious infection requiring treatment with systemically administered antibiotics at the time of study entrance, or an infection requiring systemic antibiotic therapy within 7 days prior to the first dose of study treatment.
- Pregnancy or lactation.
- Expected non-compliance.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), cardiac arrhythmia, or psychiatric illness, social situations that would limit compliance with study requirements.
- Subjects with history of another primary cancer, including co-existent second malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present or in the opinion of the investigator will not affect patient outcome.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ADI-PEG 20Investigational Medicine | Drug | ADI-PEG 20 plus Radiotherapy and Temozolomide |
| TemozolomideRadiotherapy and TMZ are standard front-line therapy for newly diagnosed GBM. | Drug | ADI-PEG 20 plus Radiotherapy and Temozolomide, Placebo plus Radiotherapy and Temozolomide |
| PlaceboInvestigational Medicine | Drug | Placebo plus Radiotherapy and Temozolomide |
Primary outcome
Overall survival (OS)
Time frame: Through study completion, 2.5 year anticipated
In the ADI-PEG 20 treated arm compared to the placebo arm, and determine if predefined patient subtypes or associated biomarkers uniquely benefit from the treatment
7 secondary outcomes
Progression-free survival (PFS)
Time frame: Through study completion, 2.5 year anticipated
Duration of response (DOR)
Time frame: Through study completion, 2.5 year anticipated
Tumor response rate
Time frame: Through study completion, 2.5 year anticipated
Safety and tolerability of ADI-PEG 20
Time frame: Through study completion, 2.5 year anticipated
Pharmacokinetics of ADI-PEG 20
Time frame: Up to week 52 or End of treatment visit
Pharmacodynamics of ADI-PEG 20
Time frame: Up to week 52 or End of treatment visit
Immunogenicity of ADI-PEG 20
Time frame: Up to week 52 or End of treatment visit
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kuo-Chen Wei, M.D. principal investigator
Chang Gung Memorial Hospital
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ADI-PEG 20 and Temozolomide in people with Glioblastoma Multiforme (GBM), run by Polaris Group at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 26 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in South Korea, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (OS) (time frame: Through study completion, 2.5 year anticipated). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2025.